{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T18:31:56Z","timestamp":1790188316269,"version":"4.1.0"},"reference-count":41,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,2,17]],"date-time":"2025-02-17T00:00:00Z","timestamp":1739750400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,2,17]],"date-time":"2025-02-17T00:00:00Z","timestamp":1739750400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003710","name":"Korea Health Industry Development Institute","doi-asserted-by":"publisher","award":["RS\u20102023\u2010KH140425(HV23C0118)"],"award-info":[{"award-number":["RS\u20102023\u2010KH140425(HV23C0118)"]}],"id":[{"id":"10.13039\/501100003710","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS\u20102024\u201000351614"],"award-info":[{"award-number":["RS\u20102024\u201000351614"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004080","name":"Korea Drug Development Fund","doi-asserted-by":"publisher","award":["1711200647\/RS\u20102022\u2010DD128921"],"award-info":[{"award-number":["1711200647\/RS\u20102022\u2010DD128921"]}],"id":[{"id":"10.13039\/501100004080","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF\u20102020M3A9D8038014"],"award-info":[{"award-number":["NRF\u20102020M3A9D8038014"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Toll\u2010like receptor 5 (TLR5) plays a critical role beyond its traditional function in innate immunity, significantly impacting metabolic regulation and liver health. Previously, we reported that TLR5 activation extends the healthspan and lifespan of aging mice. This study demonstrates that TLR5 deficiency leads to pronounced metabolic abnormalities with age, primarily affecting liver metabolic functions rather than intestinal inflammation. Comprehensive RNA sequencing analysis revealed that TLR5 deficiency induces gene expression changes in liver tissue similar to those caused by the methionine\u2013choline deficient (MCD) diet, particularly affecting lipid metabolism and circadian rhythm\u2010related genes. TLR5 knockout (TLR5 KO) mice displayed an increased propensity for liver fibrosis and lipid accumulation under the MCD diet, exacerbating liver pathology. Both hepatocytes and hepatic stellate cells in TLR5 KO mice were functionally impacted, leading to metabolic dysfunction and fibrosis. These findings suggest that TLR5 could be a significant target for addressing metabolic diseases that arise and worsen with aging. Furthermore, understanding the mechanisms by which TLR5 activation extends healthspan could provide valuable insights into therapeutic strategies for enhancing longevity and managing age\u2010related metabolic disorders.<\/jats:p>","DOI":"10.1111\/acel.70009","type":"journal-article","created":{"date-parts":[[2025,2,17]],"date-time":"2025-02-17T04:31:01Z","timestamp":1739766661000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["The Impact of Toll\u2010Like Receptor 5 on Liver Function in Age\u2010Related Metabolic Disorders"],"prefix":"10.1111","volume":"24","author":[{"given":"Dong\u2010Hyun","family":"Kim","sequence":"first","affiliation":[{"name":"MediSpan, Inc  Bundang\u2010gu Gyeonggi\u2010do Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hye Sun","family":"Go","sequence":"additional","affiliation":[{"name":"MediSpan, Inc  Bundang\u2010gu Gyeonggi\u2010do Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eun Jae","family":"Jeon","sequence":"additional","affiliation":[{"name":"MediSpan, Inc  Bundang\u2010gu Gyeonggi\u2010do Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thi Quynh Trang","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Chonnam National University Medical School  Hwasun\u2010gun Jeonnam\u2010do Republic of Korea"},{"name":"Center for Creative Biomedical Scientists Chonnam National University Medical School  Hwasun\u2010gun Jeonnam\u2010do Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Da Yeon","family":"Kim","sequence":"additional","affiliation":[{"name":"MediSpan, Inc  Bundang\u2010gu Gyeonggi\u2010do Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hansung","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Chonnam National University Medical School  Hwasun\u2010gun Jeonnam\u2010do Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyo\u2010Ji","family":"Eom","sequence":"additional","affiliation":[{"name":"MediSpan, Inc  Bundang\u2010gu Gyeonggi\u2010do Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung Young","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Konkuk University School of Medicine  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang Chul","family":"Park","sequence":"additional","affiliation":[{"name":"Future Life and Society Research Center Chonnam National University Medical School  Hwasun\u2010gun Jeonnam\u2010do Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1533-0710","authenticated-orcid":false,"given":"Kyung A","family":"Cho","sequence":"additional","affiliation":[{"name":"MediSpan, Inc  Bundang\u2010gu Gyeonggi\u2010do Republic of Korea"},{"name":"Department of Biochemistry Chonnam National University Medical School  Hwasun\u2010gun Jeonnam\u2010do Republic of Korea"},{"name":"Center for Creative Biomedical Scientists Chonnam National University Medical School  Hwasun\u2010gun Jeonnam\u2010do Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,2,17]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbalip.2014.11.013"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells11091379"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/417023"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1222805110"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2010.57"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2012.07.004"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/30.1.207"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.25.14863"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcmgh.2016.04.007"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.2147\/JIR.S407521"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41574\u2010018\u20100059\u20104"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2017.05.007"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts251"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2023.104514"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms12179"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.4254\/wjh.v8.i32.1354"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20701"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.imlet.2014.07.017"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010023\u201044263\u20102"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.14348\/molcells.2015.0213"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adm9281"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2015.017"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419\u2010021\u201003654\u20103"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.103344"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11357\u2010020\u201000186\u20100"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3461"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.21060"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41573\u2010020\u201000109\u2010w"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.2144\/03342mt01"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1101\/2024.01.04.574014"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2020.01.050"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010022\u201032552\u20101"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2011.12.017"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2017.38"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20120504"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/586939"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200737306"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/cmi.2017.122"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40779\u2010021\u201000309\u20104"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v22.i48.10512"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2019.11.012"}],"container-title":["Aging Cell"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acel.70009","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/acel.70009","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acel.70009","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T23:09:56Z","timestamp":1781132996000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/acel.70009"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,17]]},"references-count":41,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2025,6]]}},"alternative-id":["10.1111\/acel.70009"],"URL":"https:\/\/doi.org\/10.1111\/acel.70009","archive":["Portico"],"relation":{},"ISSN":["1474-9718","1474-9726"],"issn-type":[{"value":"1474-9718","type":"print"},{"value":"1474-9726","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,17]]},"assertion":[{"value":"2024-08-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-01-10","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-17","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70009"}}